This proposal will investigate whether eating frequency influences health. Evidence-based recommendations are lacking for the optimal number of daily eating occasions. This is an important area of research because over the past 40 years Americans' eating habits have changed from three meals a day to a pattern whereby most people now have 6-8 daily eating occasions. Apart from potential increases in total energy intake, frequent eating leaves people in a constant postprandial state. This constant, modestly elevated glycemia disturbs the normal glucose-insulin and counter-regulatory hormone network balance and also disturbs downstream cell signaling pathways. A constant postprandial state may increase systemic inflammation and cause numerous other metabolic disturbances. As a result, eating frequency (EF) may be associated with risk of diet-related chronic diseases such as cardiovascular disease, cancer and diabetes, which are the major causes of morbidity, mortality and health care costs in the U.S. To better understand this phenomena we propose a randomized, cross-over clinical trial to test a low-EF eating pattern (three eating occasions/day) vs. a high-EF eating pattern (six eating occasions/day) in relation to inflammation, an adipokine and appetite. We hypothesize that compared to eating three times/day, eating six times/day will increase biomarkers of systemic inflammation, will decrease a beneficial adipokine and will increase both biomarkers and self-reported measures of appetite. We will test our hypothesis with these specific aims: 1) To test the effects of low vs. high eating frequency on inflammatory biomarkers (fasting high-sensitivity C-reactive protein, Interleukin-6 and tumor necrosis factor-?,) and a beneficial adipokine (adiponectin); 2) To test the effects of low vs. high eating frequency on appetite [daily ratings of perceived appetite and serial ratings during a six-hour appetite testing session] and biomarkers involved in appetite regulation and food intake (leptin, ghrelin, peptide YY, and cholecystokinin). We will enroll n=50 males and females who are normal weight, overweight or obese. Participants will complete two 3-week long isocaloric intervention periods in random order [low EF (three eating occasions/day) and high EF (six eating occasions/day)]. Participants will be free-living and eating their own food using study-provided structured meals plans. Study staff will provide on-going support and instruction to maximize adherence to the protocol. Fasting blood samples will be collected at the beginning and end of each study phase. We will test for the intervention effect by using the GEE modification of linear regression to compare mean biomarker response (intervention effect) for each study phase. On the last day of each intervention period, participants will complete 6-hour appetite testing sessions where two test meals will be provided in the low-EF phase and four test meals will be provided in the high-EF phase. Serial appetite ratings and bloods will be collected to assess perceived appetite and hormones of appetite and satiety. Results from this investigation will be used to form guidelines for eating frequency in the context of an overall healthy diet.